ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Aug. 1988, p. 1143-1148 Vol. 32, No.

8
0066-4804/88/081143-06$02.00/0
Copyright © 1988, American Society for Microbiology

Comparative Activities of Cefuroxime, Amoxicillin-Clavulanic Acid,

Ciprofloxacin, Enoxacin, and Ofloxacin against Aerobic and
Anaerobic Bacteria Isolated from Bite Wounds
ELLIE J. C. GOLDSTEIN* AND DIANE M. CITRON
R. M. Alden Research Laboratory, Santa Monica Hospital Medical Center, Santa Monica, California 90404
Received 29 March 1988/Accepted 21 May 1988
We studied the comparative in vitro activities of 10 oral antimicrobial agents against 147 aerobic and 61
anaerobic bacteria making up species in 13 genera (Staphylococcus aureus, streptococci, Eikenella corrodens,
Pasteurella multocida, Haemophilus-Actinobacillus spp., M-5, EF-4, Moraxella spp., Flavobacterium Ilb,
Bacteroides melaninogenicus, Bacteroides spp., Fusobacterium spp., and Peptostreptococcus spp.) that were
isolated from bite wounds. Cefuroxime was generally >fourfold more active than cephalexin and cefadroxil
against all aerobic isolates, including Pasteurella multocida. The fluoroquinolones were highly active against
most aerobic isolates but were less active against anaerobic isolates. Ciprofloxacin was generally more active
than either enoxacin or ofloxacin. Discrepancies of >30% in the interpretation of susceptibilities between break
points suggested by the National Committee for Clinical Laboratory Standards and those related to oral dose
peak levels (one-half to one-quarter of maximum achievable concentrations) were noted in 14% (18 of 130) of
the instances.

The choice of an appropriate antimicrobial regimen for
infections caused by animal and human bites poses a di-
lemma for clinicians. Approximately 80% of bite wounds
harbor potential pathogens, including many unusual and
fastidious aerobic and anaerobic bacteria (10). Anaerobic
bacteria can be isolated from approximately 30 and 60% of
animal and human bite wounds, respectively (2, 6, 7, 10),
and their isolation has been associated with more severe
clinical infections (11). Yet, in an era of cost-consciousness,
these wounds are often not cultured aerobically and are
rarely cultured anaerobically except in research studies. To
compound these problems, most clinical laboratories are
unable to determine the in vitro susceptibilities of fastidious
aerobic and anaerobic bacteria that are frequently isolated
from bite wounds.
Consequently, clinicians must sometimes rely on the
medical literature to guide therapeutic choices, both empiric
and specific. Only two systematic susceptibility studies with
large numbers and varieties of bite pathogens exist in the
English language literature (2, 9). In these studies both a high
percentage of 3-lactamase-producing bacteria (2) and the
emergence of bacteria that are resistant to commonly used
antimicrobial agents have been noted in several genera of
isolates obtained from bite wounds (9). Information about
newer alternative therapeutic agents and their in vitro activ-
ities against the full spectrum of species isolated from bite
wounds is therefore needed to help guide clinicians.
Cefuroxime axetil, the new orally administered, esterified
formulation of cefuroxime, and ciprofloxacin, an oral fluo-
roquinolone antibacterial agent, have recently been ap-
proved for use in skin and soft tissue infections. Ofloxacin
and enoxacin are two other oral fluoroquinolones under
investigation that have potential use in skin and soft tissue
infections. Since these agents can be used to treat animal and
human bite wound infections, we determined the compara-
tive susceptibilities of 147 aerobic and 61 anaerobic bite
*
Corresponding author.
1143
wound isolates to these new antimicrobial agents and com-
pared their activities with the activities of the older antimi-
crobial agents that are frequently used to treat bite wound
infections.
MATERIALS AND METHODS
All bacteria studied were clinical isolates and were iden-
tified by standard criteria (1, 13, 14, 17). The sources and
numbers of isolates were as follows: dog bites, 81; cat bites,
33; human bites, 53; other animal bites, 4; and bites of
unknown origin, 20. Eighteen Flavobacterium Ilb isolates
came from the collection of John M. Pickett (University of
California, Los Angeles) and were from unknown clinical
sources. The numbers and species of the isolates tested are
given in Tables 1 and 2.
The following standard laboratory powders were supplied
by the indicated companies: penicillin and cephalexin, Eli
Lilly & Co., Indianapolis, Ind.; ampicillin, Bristol Labora-
tories, Syracuse, N.Y.; tetracycline, Pfizer Inc., New York,
N.Y.; amoxicillin-clavulanic acid, Beecham Laboratories,
Bristol, Tenn.; cefadroxil, Mead Johnson, Evansville, Ind.;
cefuroxime, Glaxo Inc., Research Triangle Park, N.C.;
ciprofloxacin, Miles Pharmaceuticals, West Haven, Conn.;
ofloxacin, Ortho Pharmaceuticals Co., Raritan, N.J.; and
enoxacin, Warner Lambert Co., Ann Arbor, Mich.
Strains were taken from frozen stock cultures and trans-
ferred twice to ensure purity and good growth. Aerobic
bacteria were tested by standard procedures by the appro-
priate methods for the particular organism (9, 14). Mueller-
Hinton agar supplemented with hemin (10 ,ug/ml) was the
basal medium used for all aerobic isolates. The media for
Eikenella corrodens and the viridans group streptococci
were supplemented with 5% sheep blood, while media for
Haemophilus spp., Actinobacillus spp., and II-J were sup-
plemented with 5% rabbit blood. Anaerobic bacteria were
cultured and inocula were prepared by the methods outlined
in the Wadsworth Anaerobic Bacteriology Manual (17).
Brucella agar supplemented with hemin, vitamin K1, and 5%
1144 GOLDSTEIN AND CITRON ANTIMICROB. AGENTS CHEMOTHER.

TABLE 1. Comparative susceptibilities of aerobic human and animal bite wound isolates to cefuroxime, amoxicillin-clavulanic acid,
ciprofloxacin, enoxacin, and ofloxacin
(,ugIml)"
MICMIC
~~~point(~~~~Lg/ml)' o% Susceptible(p.g/ml)
at the break
Organism (no.) Antibacterial agent
50% 90% NCCLS Oral
Range dose-related

Staphylococcus aureus (20) Cefuroxime 0.125-2.0 1.0 2.0 100 (8) 100 (2)
Cephalexin 1.0-4.0 4.0 4.0 100 (8) 25b (2)
Cefadroxyl 1.0-4.0 4.0 4.0 100 (8) 20b (2)
Penicillin G <0.03-16 1.0 8.0 15 (-O.1) 15 (-O.1)
Amoxicillin-clavulanic acid 50.03-1.0 0.5 1.0 100 (4, 2c) 100 (4, 2C)
Ampicillin .0.03-8.0 2.0 4.0 20 (<0.2) 20 (<0.2)
Tetracycline 0.25-64 0.5 32 85 (4) 85 (2)
Ciprofloxacin 0.25-0.5 0.5 0.5 100 (1) 100 (1)
Ofloxacin 0.125-0.5 0.25 0.5 100 (2) 100 (2)
Enoxacin 0.5-2.0 1.0 2.0 100 (2) 100 (2)
Eikenella corrodens (17) Cefuroxime 1.0-16 8.0 8.0 71 (8) 6b (2)
Cephalexin 8.0-128 32 64 6 (8) 0 (2)
Cefadroxyl 16.0-128 64 128 0 (8) 0 (2)
Penicillin G 0.12-2.0 1.0 2.0 94 (2) 94 (2)
Amoxicillin-clavulanic acid 0.12-1.0 1.0 1.0 100 (8, 4) 100 (4, 2)
Ampicillin 0.25-4.0 0.5 2.0 88 (2) 88 (2)
Tetracycline 2.0-8.0 2.0 8.0 88 (4) 7b (2)
Ciprofloxacin .0.03-0.06 .0.03 0.06 100 (1) 100 (1)
Ofloxacin 0.03-0.125 0.06 0.06 100 (2) 100 (2)
Enoxacin 0.06-0.5 0.06 0.5 100 (2) 100 (2)
Pasteurella multocida (20) Cefuroxime s0.03-0.25 0.125 0.25 100 (8) 100 (2)
Cephalexin 0.25-4.0 4.0 4.0 100 (8) 40b (2)
Cefadroxyl 0.5-16 4.0 8.0 85 (8) 5b (2)
Penicillin G s0.03-0.125 0.125 0.125 100 (2) 100 (1)
Amoxicillin-clavulanic acid s0.03-0.5 0.125 0.25 100 (8, 4) 100 (4, 2)
Ampicillin .0.03-0.25 0.125 0.25 100 (2) 100 (2)
Tetracycline 0.25-1.0 0.5 0.5 100 (4) 100 (2)
Ciprofloxacin s0.03 .0.03 <0.03 100 (1) 100 (1)
Ofloxacin .0.03-0.25 .0.03 0.06 100 (2) 100 (2)
Enoxacin <0.03-0.5 0.12 0.5 100 (2) 100 (2)
Haemophilus- Cefuroxime 0.06-2.0 0.25 2.0 100 (8) 100 (2)
Actinobacillus spp. (14) Cephalexin 0.5-16 4.0 8.0 93 (8) 36b (2)
Cefadroxyl 0.25-16 8.0 16 64 (8) 14b (2)
Penicillin G 0.06-0.5 0.25 0.5 100 (2) 100 (1)
Amoxicillin-clavulanic acid 0.06-0.5 0.25 0.5 100 (4, 2) 100 (4, 2)
Ampicillin 0.06-0.5 0.25 0.5 100 (2) 100 (2)
Tetracycline 0.5-4.0 2.0 4.0 100 (4) 71b (2)
Ciprofloxacin .0.03-0.06 .0.03 0.06 100 (1) 100 (1)
Ofloxacin s0.03-0.25 0.06 0.06 100 (2) 100 (2)
Enoxacin 0.03-1.0 0.12 0.5 100 (2) 100 (2)
M-5 (10) Cefuroxime 0.5-1.0 0.5 0.5 100 (8) 100 (2)
Cephalexin 4.0 4.0 4.0 100 (8) ob (2)
Cefadroxyl 4.0-8.0 4.0 8.0 50 (8) ob (2)
Penicillin G 0.125-0.25 0.25 0.25 100 (2) 100 (1)
Amoxicillin-clavulanic acid 0.125-0.25 0.125 0.25 100 (8, 4) 100 (4, 2)
Ampicillin 0.125-0.25 0.125 0.25 100 (2) 100 (2)
Tetracycline 0.5-0.5 0.5 0.5 100 (4) 100 (2)
Ciprofloxacin s0.03 .0.03 .0.03 100 (1) 100 (1)
Ofloxacin s0.03 <0.03 .0.03 100 (2) 100 (2)
Enoxacin 0.12 0.12 0.12 100 (2) 100 (2)
EF-4 (13) Cefuroxime 0.25-16.0 0.5 16 77 (8) 77 (2)
Cephalexin 2.0-16.0 4.0 16 69 (8) 15b (2)
Cefadroxyl 2.0-8.0 4.0 8.0 100 (8) 8b (2)
Penicillin G 0.125-2.0 0.125 2.0 100 (2) 92 (1)
Amoxicillin-clavulanic acid 0.125-0.5 0.25 0.5 100 (8, 4) 100 (4, 2)
Ampicillin 0.03-1.0 0.125 0.5 100 (2) 100 (2)
Tetracycline 0.5-4.0 0.5 2.0 100 (4) 85 (2)
Ciprofloxacin .0.03-0.6 .0.03 0.06 100 (1) 100 (1)
Orfloxacin .0.03-0.6 .0.03 0.06 100 (2) 100 (2)
Enoxacin 0.06-0.25 0.06 0.25 100 (2) 100 (2)
Continued on following page
VOL. 32, 1988 COMPARATIVE ACTIVITIES AGAINST BITE WOUND BACTERIA 1145

TABLE 1-Continued
% Susceptible at the break
Organism (no.) Antibacterial agent
MICMIC(i...Wml)a
(>Lg/ml)' ~~~~~point (p.g/ml)
Range 50% 90% NCCLS Oral

Streptococcus spp. (26) Cefuroxime s0.03-2.0 0.25 2.0 100 (8) 100 (2)
Cephalexin 0.06-16 4.0 8.0 96 (8) 19b (2)
Cefadroxyl 0.06-8.0 4.0 8.0 100 (8) 19b (2)
Penicillin G -0.03-0.25 0.06 0.12 96 (-0.1) 96 ('0.1)
Amoxicillin-clavulanic acid s0.03-i.0 0.06 0.12 100 (4, 2) 100 (4, 2)
Ampicillin -0.03-0.25 0.06 0.12 96 ('0.1) 96 ('0.1)
Tetracycline 0.25-32 0.5 16 73 (4) 73 (2)
Ciprofloxacin 0.25-8.0 1.0 4.0 58 (1) 58 (1)
Ofloxacin 0.25-4.0 1.0 4.0 73 (2) 73 (2)
Enoxacin 4.0-32 8.0 32 0 (2) 0 (2)
Moraxella spp. (6) Cefuroxime 0.06-8.0 0.125 100 (8) 83 (2)
Cephalexin 0.25-8.0 4.0 83 (8) 33b (2)
Cefadroxyl 0.125-4.0 4.0 100 (8) 33b (2)
Penicillin G s0.03-4.0 0.06 83 (2) 83 (1)
Amoxicillin-clavulanic acid 0.03-1.0 0.125 100 (8, 4) 100 (4, 2)
Ampicillin s0.03-2.0 0.06 100 (2) 100 (2)
Tetracycline 0.5-4.0 0.5 100 (4) 83 (2)
Ciprofloxacin s0.03-0.25 '0.03 100 (1) 100 (1)
Ofloxacin 0.03-0.125 s0.03 100 (2) 100 (2)
Enoxacin 0.12-0.5 0.12 100 (2) 100 (2)
Flavobacterium IIB (18) Cefuroxime 1->128 >128 >128 6 (8) 6 (2)
Cephalexin 8->128 >128 >128 6 (8) 0 (2)
Cefadroxyl 8->128 >128 >128 6 (8) 0 (2)
Penicillin G 2->128 >128 >128 6 (2) 0 (1)
Amoxicillin-clavulanic acid 1.0-32 32 32 11 (8, 4) 6 (4, 2)
Ampicillin 1.0->128 >128 >128 6 (2) 6 (2)
Tetracycline 4.0-32 16.0 32 29 (4) 0 (2)
Ciprofloxacin 0.5-1.0 0.5 0.5 100 (1) 100 (1)
Ofloxacin 0.25-2.0 0.25 1.0 100 (2) 100 (2)
Enoxacin 0.5-4.0 1.0 2.0 94 (2) 94 (2)

a MICs for 50 and 90% of isolates tested are indicated.

b Discrepancy of .30% between NCCLS and oral dose-related break points.
c First and second values are for amoxicillin and clavulanic acid, respectively.

laked sheep blood was the basal medium used for anaerobic
isolates.
The plates were inoculated with a Steers replicator (Craft
Machine Inc., Chester, Pa.). The inoculum used for aerobic
bacteria was 104 CFU per spot, and the inoculum used for
anaerobic bacteria and Eikenella corrodens was 105 CFU per
spot. Control plates without antimicrobial agents were inoc-
ulated before and after each series of drug-containing plates
were inoculated. Care was taken to avoid drug carry-over for
the fluoroquinolones tested. Plates with aerobic isolates
were incubated at 35°C in an aerobic environment for 24 h
and were then examined. Eikenella corrodens, viridans
group streptococci, Haemophilus spp., Actinobacillus spp.,
and II-J were incubated in 5 to 10% CO2 for 48 h and were
then examined. Anaerobic bacteria were incubated for 48 h
in jars (GasPak; BBL Microbiology Systems, Cockeysville,
Md.) and were then examined. Control strains of Staphylo-
coccus aureus ATCC 25923, Escherichia coli ATCC 25922,
Streptococcus faecalis ATCC 29212, Bacteroides thetaio-
taomicron ATCC 29741, Bacteroides fragilis ATCC 25285,
and Eikenella corrodens ATCC 23834 were tested simulta-
neously with the appropriate plates and environments.
RESULTS
The results of this study are summarized in Tables 1 and 2.
In addition to reporting the MICs for 50 and 90% of strains
tested for each species, we also report the percentage of
isolates that were susceptible at the National Committee for
Clinical Laboratory Standards (NCCLS) recommended
break point (R. N. Jones, Antimicrob. Newsl. 31:1-8, 1986)
and at a break point representing one-half to one-quarter of
the achievable peak concentrations in serum following a
usual maximum oral dose of the antimicrobial agent (14, 15).
Discrepancies between the two break points occurred with
some drugs, because the NCCLS standards are often based
on levels of an agent that are achieved after parenteral
administration, and we were interested in the levels that
related to oral doses since most bite wounds are treated with
oral antimicrobial agents. A total of 18 (14%) discrepancies
of >30% in the interpretation of the susceptibilities of
isolates are indicated in Tables 1 and 2.
On a weight basis, cefuroxime was generally >fourfold
more active than cephalexin and cefadroxil against all aero-
bic isolates (8 of 10 species), except for Flavobacterium IlIb
isolates, for which the MICs of all three cephalosporin
1146 GOLDSTEIN AND CITRON ANTIMICROB. AGENTS CHEMOTHER.

TABLE 2. Comparative susceptibilities of anaerobic human and animal bite wound isolates to cefuroxime, amoxicillin-clavulanic acid,
ciprofloxacin, enoxacin, and ofloxacin

~~~point
MICMIC(~~~.Lg/mlY'
(Rlg/ml)' 5o% Susceptible(ILg/ml)
at the break
Organism (no.) Antibacterial agent
Oral
Range 50S lo 905% NCCLS dose-related
Bacteroides melaninogenicus Cefuroxime .0.03-8.0 0.06 8.0 100 (8) 69b (2)
group (16) Cephalexin .0.03-2.0 0.5 2.0 100 (8) 100 (2)
Cefadroxyl 0.06-0.5 0.5 0.5 100 (8) 100 (2)
Penicillin G <0.03-8.0 .0.03 8.0 75 (2) 69 (1)
Amoxicillin-clavulanic acid .0.03-0.25 s0.03 0.12 100 (8, 4C) 100 (4, 2c)
Ampicillin 0.06-4.0 0.06 4.0 88 (2) 88 (2)
Tetracycline 0.125-32 0.5 4.0 94 (4) 88 (2)
Ciprofloxacin 0.06-2.0 0.25 1.0 94 (1) 94 (1)
Ofloxacin 0.125-2.0 0.5 2.0 100 (2) 100 (2)
Enoxacin 0.25-16 4.0 8.0 19 (2) 19 (2)
Bacteroides spp. (17) Cefuroxime 0.06-32 0.25 32 94 (8) 88 (2)
Cephalexin 0.5-16 2.0 8.0 94 (8) 76 (2)
Cefadroxyl 0.5-8.0 1.0 8.0 100 (8) 88 (2)
Penicillin G .0.03-32 0.12 8.0 88 (2) 82 (1)
Amoxicillin-clavulanic acid <0.03-0.5 0.06 0.5 100 (8, 4) 100 (4, 2)
Ampicillin <0.03-16 0.06 8.0 88 (2) 88 (2)
Tetracycline 0.25-64 0.5 16 82 (4) 82 (2)
Ciprofloxacin 0.06-32 1.0 2.0 82 (1) 82 (2)
Ofloxacin 0.25-16 1.0 2.0 94 (2) 94 (2)
Enoxacin 2.0-32 8.0 16 12 (2) 12 (2)
Fusobacterium spp. (18) Cefuroxime .0.03-0.5 0.25 0.5 100 (8) 100 (2)
Cephalexin 0.06-2.0 0.25 1.0 100 (8) 100 (2)
Cefadroxyl 0.06-2.0 0.5 2.0 100 (8) 100 (2)
Penicillin G '0.03-1.0 0.06 0.5 100 (2) 100 (1)
Amoxicillin-clavulanic acid <0.03-0.12 0.06 0.12 100 (8, 4) 100 (4, 2)
Ampicillin .0.03-4.0 0.06 4.0 83 (2) 83 (2)
Tetracycline 0.06-2.0 0.5 2.0 100 (4) 100 (2)
Ciprofloxacin 0.25-32 2.0 32 33 (1) 33 (1)
Ofloxacin 0.5-64 2.0 64 50 (2) 50 (2)
Enoxacin 0.25-32 16 32 6 (2) 6 (2)
Peptostreptococcus spp. (10) Cefuroxime 0.06-4.0 0.25 4.0 100 (8) 80 (2)
Cephalexin 0.25-128 2.0 32 60 (8) 50 (2)
Cefadroxyl 0.06-128 2.0 32 60 (8) 60 (2)
Penicillin G .0.03-0.5 .0.3 0.25 100 (2) 100 (1)
Amoxicillin-clavulanic acid 0.03-1.0 0.06 0.5 100 (8, 4) 100 (4, 2)
Ampicillin 0.03-1.0 0.06 0.5 100 (2) 100 (2)
Tetracycline 0.25-64 1.0 32 60 (4) 50 (2)
Ciprofloxacin s0.03-8.0 1.0 2.0 80 (1) 80 (1)
Ofloxacin .0.03-8.0 1.0 4.0 80 (2) 80 (2)
Enoxacin 0.125-32.0 4.0 8.0 20 (2) 20 (2)
a MICs for 50 and 90% of isolates tested are indicated.
I
Discrepancy of .30% between NCCLS and oral dose-related break points.
c First and second values are for amoxicillin and clavulanic acid, respectively.

agents for 50% of strains tested were >128 ,ug/ml. Cefurox-
ime was active against all Pasteurella multocida isolates at a
MIC of <0.25 ,ug/ml. Cephalexin and cephadroxil had MICs
of 4 and 8 pg/ml, respectively, for 90% of strains tested. By
using NCCLS break points, almost all Pasteurella multocida
isolates were found to be susceptible to both agents; how-
ever, by using the oral break points, 60% of isolates were
found to be resistant to cephalexin and 95% were found to be
resistant to cefadroxil. Cefuroxime had activity comparable
against anaerobic bacteria to those of cephalexin and cefa-
droxil, with the peptostreptococci showing the greatest
percentage of resistance to all three cephalosporins.
The fluoroquinolones (ciprofloxacin, enoxacin, and oflox-
acin) that were tested showed high degrees of activity
against all aerobic isolates except for the streptococci, which
were frequently resistant to all three fluoroquinolones. The
fluoroquinolones were relatively less active against the an-
aerobic bacteria compared with their activity against the
aerobic bacteria. Enoxacin was the least active fluoroquino-
lone, and a majority of all anaerobic isolates of all genera
were resistant. Ciprofloxacin and ofloxacin had comparable
activities. The fusobacteria were generally resistant to the
fluoroquinolones.
Penicillin G was active against streptococci, EF-4, M-5,
II-J, Eikenella corrodens, Haemophilus-Actinobacillus spp.,
and Pasteurella multocida. One strain of Eikenella corro-
dens and one strain of Moraxella sp. were relatively resistant
to penicillin G, for both of which the MICs were 4 pug/ml. As
expected, Flavobacterium IIb and Staphylococcus aureus
isolates were generally resistant to penicillin G. Against the
anaerobic bacteria tested, resistance to penicillin G was seen
in 31% of the Bacteroides melaninogenicus group and 18%
VOL. 32, 1988 COMPARATIVE ACTIVITIES AGAINST BITE WOUND BACTERIA
of other non-Bacteroides fragilis species in the genus Bac-
teroides. The fusobacteria and peptostreptococci tested
were all susceptible to penicillin G. Amoxicillin-clavulanic
acid was active against all aerobic and anaerobic isolates at
<1 ,ug/ml. It was not active against Flavobacterium Ilb,
which was generally resistant. Tetracycline was generally
active against all aerobic genera and many of the anaerobic
genera tested. The three strains of II-J tested (data not
shown) were generally susceptible to all the agents tested.
DISCUSSION
While some clinicians advocate the use of oral cephalo-
sporins such as cephalexin or cefadroxil for bite wounds (4),
clinical failures are increasingly reported (5, 12, 18). Several
in vitro studies, including this one, have noted a high
percentage of resistance of bacterial species typically found
in bite wounds (2, 8, 9, 16). Weber et al. (18) have noted that
cephalexin and cefaclor do not achieve levels in blood that
are sufficient to treat Pasteurella multocida infections reli-
ably. In contrast, based on its in vitro activity against clinical
isolates, cefuroxime appears to have potential clinical utility
in the therapy of bite wounds. Cefuroxime was generally
fourfold more active than cephalexin and cefadroxil, result-
ing in what should be inhibitory concentrations at a clinically
achievable level. In mixed aerobic-anaerobic bite wound
infections, either susceptibility studies should be performed
when cefuroxime is used or clinical response should be
watched carefully, since some anaerobic bacteria have been
found to be resistant to cefuroxime.
In 18 of 130 (14%) instances, there were discrepancies of
>30% in the susceptibility interpretation between the
NCCLS criteria (Jones, Antimicrob. Newsl.) and those
based on achievable oral levels of antimicrobial agents (14,
15). These occurred almost exclusively with the cephalospo-
rins, particularly cephalexin and cefadroxil. Streptococci,
Haemophilus-Actinobacillus spp., M-5, Staphylococcus au-
reus, Moraxella spp., EF-4, and Pasteurella multocida iso-
lates were regarded as susceptible by NCCLS criteria and
resistant by oral level criteria. This underscores the impor-
tance of creating separate break points for the oral and
parenteral usage of antimicrobial agents. In support of this
result is our own clinical experience, which has shown that
the treatment of human bite wounds and clenched fist
injuries with cephalexin may lead to therapeutic failure
because of the presence of a combination of viridans group
streptococci and Eikenella corrodens (5; unpublished data).
Since cefuroxime was considerably more active than ceph-
alexin and cefadroxil, there were only two instances, one
with a strain of Eikenella corrodens and one with a strain of
Bacteroides melaninogenicus, in which discrepancies were
found.
The fluoroquinolones were generally very active against
all aerobic isolates, including Flavobacterium Ilb. However,
they were deficient in their activities against aerobic strep-
tococci. Streptococci are the bacteria that are most fre-
quently isolated from bite wounds, usually in mixed cultures
(10). Their role as synergistic pathogens with Eikenella
corrodens has been documented (3), while their role either as
primary pathogens or as synergistic pathogens with other
species remains to be evaluated. The fluoroquinolones were
also relatively inactive against many anaerobic bacteria.
Consequently, their use in the treatment of bite wounds is
also problematic and will require additional clinical evalua-
tions.
Resistance to penicillin G was seen in seven genera,
including 31% of the Bacteroides melaninogenicus and 18%
1147
of other Bacteroides spp. This confirms the data of Brook
(2), who recovered P-lactamase-producing organisms in 41%
(16 of 39) of cases, including 12 of 17 bite wounds treated
with penicillin. Brook (2) has also noted that two of five
Bacteroides melaninogenicus strains and one of three Bac-
teroides oralis strains that were isolated produced ,-lac-
tamases. Results of a previous study from our laboratory (9)
noted that all the Bacteroides species isolated from animal
bite wounds were penicillin susceptible, while 47% (7 of 15)
isolated from human bite wounds produced P-lactamase and
were penicillin resistant. In the present study, resistance of
most anaerobic bacteria to penicillin G was found in human
bite wound isolates; one Bacteroides melaninogenicus iso-
lated from a cat bite wound produced P-lactamase and was
penicillin resistant.
Amoxicillin-clavulanic acid has been shown to be clini-
cally effective in the treatment of bite wound infections (11)
and is considered by some to be the drug of choice for
empiric therapy. Our in vitro data confirm its activity against
almost all species of bacteria found in bite wounds. We did
not encounter the development of any resistance to amoxi-
cillin-clavulanic acid in bite wound isolates, despite its
extensive use for the treatment of infections in these
wounds. Only Flavobacterium Ilb was resistant to amoxicil-
lin-clavulanic acid.
Tetracycline had good in vitro activity against most iso-
lates and, along with the expanded-spectrum agents of
doxycycline and minocycline, offers potential utility as a
therapeutic alternative in penicillin-allergic patients.
ACKNOWLEDGMENTS
We thank Alice E. Goldstein, Judee H. Knight, Gregory B.
Ferguson, John M. Pickett, and Sydney M. Finegold for various
forms of assistance. In addition, we acknowledge the assistance and
cooperation of the microbiology technologists of Santa Monica
Hospital Medical Center and St. Johns Hospital Health Center for
the primary isolations.
This study was supported, in part, by grants from Glaxo Inc.,
Beecham Laboratories, Ortho Pharmaceutical Co., and the Maurice
Goldstein Public Health Research Fund.
LITERATURE CITED
1. Blachman, U., and M. J. Pickett. 1978. Unusual aerobic bacilli in
clinical bacteriology. Scientific Development Press, Los
Angeles.
2. Brook, I. 1987. Microbiology of human and animal bite wounds
in children. Pediatr. Infect. Dis. J. 6:29-32.
3. Brooks, G. F., J. M. O'Donoghue, J. W. Smith, J. P. Rissing, K.
Soapes, and J. W. Smith. 1974. Eikenella corrodens, a recently
recognized pathogen. Medicine 53:325-342.
4. Callaham, M. 1980. Prophylactic antibiotics in common dog bite
wounds: a controlled study. Ann. Emerg. Med. 9:410(414.
5. Goldstein, E. J. C., M. Barones, and T. A. Miller. 1983.
Eikenella corrodens in hand infections. J. Hand Surg. 8:563-
567.
6. Goldstein, E. J. C., D. M. Citron, and S. M. Finegold. 1980. Dog
bite wounds and infection: a prospective clinical study. Ann.
Emerg. Med. 9:508-512.
7. Goldstein, E. J. C., D. M. Citron, and S. M. Finegold. 1984. Role
of anaerobic bacteria in bite wound infections. Rev. Infect. Dis.
6:S177-S183.
8. Goldstein, E. J. C., D. M. Citron, and G. A. Richwald. 1988.
Lack of in vitro efficacy of oral forms of certain cephalosporins,
erythromycin, and oxacillin against Pasteurella multocida. An-
timicrob. Agents Chemother. 32:213-215.
9. Goldstein, E. J. C., D. M. Citron, A. E. Vagvolgyi, and S. M.
Finegold. 1986. Susceptibility of bite wound bacteria to seven
1148 GOLDSTEIN AND CITRON
oral antimicrobial agents, including RU-985, a new erythromy-
cin: considerations in choosing empiric therapy. Antimicrob.
Agents Chemother. 29:556-559.
10. Goldstein, E. J. C., D. M. Citron, B. Wield, U. Blachman, V. L.
Sutter, T. A. Miller, and S. M. Finegold. 1978. Bacteriology of
human and animal bite wounds. J. Clin. Microbiol. 8:667-672.
11. Goldstein, E. J. C., J. F. Reinhardt, P. M. Murray, and S. M.
Finegold. 1987. Outpatient therapy of bite wounds: demographic
data, bacteriology, and a prospective, randomized trial of amox-
icillin/clavulanic acid versus penicillin +/- dicloxacillin. Int. J.
Dermatol. 26:123-127.
12. Goldstein, R. W., G. L. Goodhart, and J. E. Moore. 1986.
Pateurella multocida infection after animal bite. N. Engl. J.
Med. 315:460.
13. Holdeman, L. V., E. P. Cato, and W. E. C. Moore (ed.). 1977.
Anaerobe laboratory manual, 4th ed. Virginia Polytechnic In-
stitute and State University, Blacksburg.
14. Lennette, E. H., A. Balows, W. J. Hausler, Jr., and H. J.
ANTIMICROB. AGENTS CHEMOTHER.
Shadomy (ed.). 1985. Manual of clinical microbiology, 4th ed.,
p. 143-192, 309-349, 387-393, 967-977. American Society for
Microbiology, Washington, D.C.
15. Norris, S. M., and G. L. Mandell. 1985. Tables of antimicrobial
agent pharmacology, p. 308-332. In G. L. Mandell, R. G.
Douglas, Jr., and J. E. Bennett (ed.), Principles & practice of
infectious diseases, 2nd ed. John Wiley & Sons, Inc., New
York.
16. Shikuma, C. C., and G. D. Overturf. 1985. Antibiotic suscepti-
bility of Pasteurella multocida. Eur. J. Clin. Microbiol. 4:518-
519.
17. Sutter, V. L., D. M. Citron, M. A. C. Edelstein, and S. M.
Finegold. 1985. Wadsworth anaerobic bacteriology manual, 4th
ed. Star Publishing Co., Belmont, Calif.
18. Weber, D. J., J. S. Wolfson, M. N. Swartz, and D. C. Hooper.
1984. Pasteurella multocida infections: report of 34 cases and
review of the literature. Medicine 63:133-154.